Cell surface adherence reactions are of central importance in the biology of lymphocytes, monocytes, and granulocytes. The LFA-1 (lymphocyte function-associated) and Mac-1 molecules mediate different types of adhesion reactions on these cells LFA-1 participates in T lymphocyte and natural killer cell adhesion to target cells. The Mac-1 antigen is the complement receptor type 3, which mediates adhesion monocytes and granulocytes to C3bi-sensitized particles. LFA-1 and Mac-1 are structurally related glycoproteins, each containing two subunits noncovalently associated in Alpha1 Beta1 complexes. Peptide mapping and serological reactivity have demonstrated that the 180,000 Mr and 170,000 Mr Alpha chains of LFA-1 and Mac-1, respectively, are distinct polypeptides and that the 95,000 Mr beta chains are probably identical. We have determined the N-terminal amino acid sequence of the Alpha-subunits of LFA-1 and Mac-1, and the sequence homologies observed suggest that the Alpha subunits are members of a novel leukocyte adhesion protein family. A search for similarities to previously sequenced proteins has revealed a further, unexpected homology between LFA-1 and leukocyte (Alpha) interferons. We plan to continue our analysis of the LFA-1/Mac-1 family of molecules by cloning and sequencing portions of these genes. We have used synthetic DNA probes to isolate a clone presumed to contain the 5' coding sequence of the Mac-1 Alpha chain. We will use the same approach to isolate clones of the LFA-1 alpha chain gene. The DNA sequence data will provide important information concerning the structural and functional relationships between LFA-1 and Mac-1 and may aid in understanding the mechanisms that govern the lineage specific expression of their Alpha chains with the common Beta chain. We will also use cloned DNA sequences as probes to search for other members of this superfamily and to study gene organization and chromosomal location.